POS0223 LONG-TERM SURVEILLANCE STUDY OF RITUXIMAB (MABTHERA)-TREATED PATIENTS WITH GRANULOMATOSIS WITH POLYANGIITIS (GPA) OR MICROSCOPIC POLYANGIITIS (MPA): RITUXIMAB SURVEILLANCE STUDY IN VASCULITIS (RIVAS)
Authors: L. Uchida, C. Loechel, M. Nodale, S. Bond, D. Jayne
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Rituximab is used for remission induction, and for the prevention of relapse in ANCA-associated vasculitis (AAV). However, the long-term safety of rituximab in the real-world setting remains unclear. <h3>Objectives</h3> To evaluate the incidence of safety events (serious adverse events and adverse events of special interest) and risk profile of rituximab and to compare the time to first safety event between a rituximab cohort and a cohort treated with other therapies over 6 months to 15 years from first exposure. <h3>Methods</h3> RIVAS was a retrospective, observational study including patients with GPA/MPA who had received rituximab (MabThera) or other treatments between 2003 and 2018 at Addenbrooke's hospital, Cambridge, UK. Clinical and laboratory variables were collected at baseline and every 12-18 months until 30 September 2018. To calculate the time to event, Time 0 was defined as either initiation of MabThera treatment for the rituximab cohort or the time of first disease flare/diagnosis for the control cohort. The primary endpoint was the time to first safety event. Key secondary endpoints were time to first pre-categorized safety event such as serious infection and cardiovascular disorders. The time to second safety event was an exploratory endpoint. <h3>Results</h3> 392 GPA/MPA patients were enrolled: 247 in the rituximab and 145 in the control cohort with a total of 2,217 person-years (mean study duration 5.7 years). Mean age was 61 years, 52% were female, 77% had GPA and 23% MPA. The mean disease duration at baseline was 55.3 months (SD 70.2) in the rituximab, while 33.3 months (SD 63.8) in the control arm. Baseline characteristics were not matched between groups reflecting the predominant use of rituximab for relapsing or refractory disease. Five hundred and thirty-three safety events occurred in 164 patients (66%) in the rituximab and 170 in 78 patients (54%) in the control group. Sixty-seven patients (27%) in the rituximab group and 19 patients (13%) in the control group experienced serious infection (Table 1). Thirty patients (12%) in the rituximab group developed severe hypogammaglobulinemia (IgG &lt;3 g/l) requiring treatment/change of treatment or hypogammaglobulinemia requiring IVIg and 19 (8%) received IVIg compared to 3 (2%) and 1 (0.7%) patient in the control group. There were no differences in incidence rates for malignancy, cardiovascular events or renal insufficiency between groups. There was no difference in the time to first safety event between groups (HR 1.32, 95%CI 0.952-1.83, p=0.096), nor in the time to first pre-categorized safety event. However, a shorter time to second safety event was observed in the rituximab group (HR 1.98, 95%CI 1.25-3.13, p=0.004) (Figure 1). Predictors of safety events were older age, higher vasculitis damage scores and chronic pulmonary and renal disease. The relative risk of serious infection was higher in the rituximab group (unadjusted relative risk (RR) 2.07; 95%CI 1.30-3.30). <h3>Conclusion</h3> Over 60% of patients with GPA/MPA experienced a safety event in their disease course. Rituximab did not increase the risk of experiencing a first safety event but the time to second safety event was shorter in the rituximab group. Limitations of the trial design do not permit firm conclusions concerning differences between treatment groups. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Lisa Uchida: None declared, Claudia Loechel: None declared, Marianna Nodale: None declared, Simon Bond: None declared, David Jayne Shareholder of: Aurinia, Speakers bureau: GSK, CSL Vifor, Consultant of: Astra-Zeneca, Chemocentryx, GSK, Novartis, Roche, Takeda, CSL Vifor, Grant/research support from: GSK, Roche.